scholarly journals Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal Models

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Xueli Fan ◽  
Hongliang Zhang ◽  
Yun Cheng ◽  
Xinmei Jiang ◽  
Jie Zhu ◽  
...  
Keyword(s):  
Animal Models ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Disease Development ◽  
Cell Type ◽  
Organ Specific ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages ◽  
Lines Of Evidence

Macrophages are important immune cells of the innate immune system that are involved in organ-specific homeostasis and contribute to both pathology and resolution of diseases including infections, cancer, obesity, atherosclerosis, and autoimmune disorders. Multiple lines of evidence point to macrophages as a remarkably heterogeneous cell type. Different phenotypes of macrophages exert either proinflammatory or anti-inflammatory roles depending on the cytokines and other mediators that they are exposed to in the local microenvironment. Proinflammatory macrophages secrete detrimental molecules to induce disease development, while anti-inflammatory macrophages produce beneficial mediators to promote disease recovery. The conversion of the phenotypes of macrophages can regulate the initiation, development, and recovery of autoimmune diseases. Human neuroimmune diseases majorly include multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) and macrophages contribute to the pathogenesis of these neuroimmune diseases. In this review, we summarize the double roles of macrophage in neuroimmune diseases and their animal models to further explore the mechanisms of macrophages involved in the pathogenesis of these disorders, which may provide a potential therapeutic approach for these disorders in the future.

scholarly journals Anti-inflammatory macrophages improve skeletal muscle recovery from ischemia-reperfusion

2015 ◽  
Vol 118 (8) ◽  
pp. 1067-1074 ◽  
Author(s):  
David W. Hammers ◽  
Viktoriya Rybalko ◽  
Melissa Merscham-Banda ◽  
Pei-Ling Hsieh ◽  
Laura J. Suggs ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Innate Immune System ◽  
Ischemia Reperfusion ◽  
Innate Immune ◽  
Therapeutic Approaches ◽  
Muscle Recovery ◽  
Igf I ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages ◽  
Whole Muscle

The presence of macrophages (MPs) is essential for skeletal muscle to properly regenerate following injury. The aim of this study was the evaluation of MP profiles and their importance in skeletal muscle recovering from tourniquet-induced ischemia-reperfusion (I/R). Using flow cytometry, we identified two distinct CD11b+ MP populations that differ in expression of the surface markers Ly-6C and F4/80. These populations are prominent at 3 and 5 days of reperfusion and molecularly correspond to inflammatory and anti-inflammatory MP phenotypes. Sorted MP populations demonstrated high levels of IGF-I expression, and whole muscle post-I/R IGF-I expression strongly correlates with F4/80 expression. This suggests MPs largely influence postinjury IGF-I upregulation. We additionally demonstrate that direct intramuscular injection of FACS-isolated CD11b+Ly-6CloF4/80hi MPs improves the functional and histological recovery of I/R-affected muscle. Taken together, these data further support the substantial influence of the innate immune system on muscle regeneration and suggest MP-focused therapeutic approaches may greatly facilitate skeletal muscle recovery from substantial injury.

scholarly journals Hydroalcoholic extract from Origanum vulgare induces a combined anti-mycobacterial and anti-inflammatory response in innate immune cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213150 ◽  
Author(s):  
Federica De Santis ◽  
Noemi Poerio ◽  
Angelo Gismondi ◽  
Valentina Nanni ◽  
Gabriele Di Marco ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Origanum Vulgare ◽  
Hydroalcoholic Extract ◽  
Anti Inflammatory

scholarly journals An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease

1998 ◽  
Vol 187 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Benjamin M. Segal ◽  
Bonnie K. Dwyer ◽  
Ethan M. Shevach
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Innate Immune System ◽  
Demyelinating Disease ◽  
Critical Role ◽  
Interferon Γ ◽  
Innate Immune ◽  
Th Cell ◽  
Organ Specific ◽  
Cytokine Networks

Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon γ. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.

Four Reasons to Consider a Novel Class of Innate Immune Molecules in the Oral Epithelium

2003 ◽  
Vol 82 (12) ◽  
pp. 944-950 ◽  
Author(s):  
E.E. LeClair
Keyword(s):  
Host Defense ◽  
Innate Immune System ◽  
Physiological Response ◽  
Three Dimensional ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Defense Protein ◽  
Lines Of Evidence

An expanding number of innate immune molecules occupy the “epithelial frontier”. This review introduces a recently recognized class of mammalian proteins with similarity to PLUNC (palate, lung and nasal epithelium clone), which is itself related to the host defense protein BPI (bactericidal/permeability-increasing protein). Four emerging lines of evidence unite the PLUNC-like proteins: conserved genetic structure, epithelial expression, three-dimensional protein similarity, and a physiological response to injury or inflammation. By analogy to known proteins of the innate immune system, an emerging hypothesis for this family is that they act as sensors of Gram-negative bacteria in the oral cavity, among other areas.

scholarly journals The IκB-Protein BCL-3 Controls MAPK Activity by Promoting TPL-2 Degradation in the Nucleus

2018 ◽  
Author(s):  
Patricia E. Collins ◽  
Domenico Somma ◽  
David Kerrigan ◽  
Felicity Herrington ◽  
Karen R. Keeshan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Primary Site ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Nucleocytoplasmic Shuttling ◽  
Activation Threshold ◽  
Invasive Pathogens ◽  
Mapk Activity

AbstractThe ability of the innate immune system to distinguish between low level microbial presence and invasive pathogens is fundamental for immune homeostasis and immunity. However, the molecular mechanisms underlying threat discrimination by innate immune cells are not clearly defined. Here we describe the integration of the NF-ĸB and MAPK pathways in the nucleus by the IĸB protein BCL-3 and the MAP3K TPL-2. Our data reveals that TPL-2 is a nucleocytoplasmic shuttling protein and demonstrates that the nucleus is the primary site for TPL-2 ubiquitination and proteasomal degradation. BCL-3 promotes TPL-2 degradation through interaction in the nucleus. As a consequence, Bcl3-/- macrophages have increased TPL-2 stability and MAPK activity following TLR stimulation. The enhanced stability of TPL-2 in Bcl3-/- macrophages lowers the MAPK activation threshold and the level of TLR ligand required to initiate an inflammatory response. This study establishes the nucleus as a key regulatory site for TLR-induced MAPK activity and identifies BCL-3 as a regulator of the cellular decision to initiate inflammation

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

scholarly journals Immune cells—A curse and a blessing!

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Valbona Mirakaj
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
The Impact

Innate immune cells are crucial in the development and regulation of cardiovascular disease. In this issue, two groups, Davis et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201839) and Li et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210008) describe the impact of the innate immune system on the development of cardiovascular disease.

scholarly journals TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Ser877

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ricardo J. Antonia ◽  
Johnny Castillo ◽  
Laura E. Herring ◽  
D. Stephen Serafin ◽  
Pengda Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Innate Immune System ◽  
Innate Immune ◽  
Cellular Growth ◽  
Phosphorylation Sites ◽  
Cell Type ◽  
Mechanistic Target Of Rapamycin ◽  
Mtor Complex 1 ◽  
Mtor Activity

Abstract While best known for its role in the innate immune system, the TANK-binding kinase 1 (TBK1) is now known to play a role in modulating cellular growth and autophagy. One of the major ways that TBK1 accomplishes this task is by modulating the mechanistic Target of Rapamycin (mTOR), a master regulator that when activated promotes cell growth and inhibits autophagy. However, whether TBK1 promotes or inhibits mTOR activity is highly cell type and context dependent. To further understand the mechanism whereby TBK1 regulates mTOR, we tested the hypothesis that TBK1 phosphorylates a key component of the mTOR complex 1 (mTORC1), Raptor. Using kinase assays coupled with mass spectrometry, we mapped the position of the TBK1 dependent phosphorylation sites on Raptor in vitro. Among the sites identified in vitro, we found that TBK1 promotes Raptor Ser877 phosphorylation in cells both basally and in response to pathogen-associated molecules known to induce TBK1 activity. The levels of Raptor Ser877 phosphorylation were inversely correlated with the levels of mTOR activity. Expression of a mutant Raptor that could not be phosphorylated at Ser877 led to an increase in mTORC1 activity. We conclude that TBK1 limits mTORC1 activity by promoting Raptor Ser877 phosphorylation.

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

O-022 YI Innate Immune IL10 Receptor Signaling Regulates Mucosal Homeostasis and the Function of Anti-inflammatory Macrophages

2013 ◽  
Vol 19 ◽  
pp. S14-S15
Author(s):  
Dror Shouval ◽  
Amlan Biswas ◽  
Jeremy Goettel ◽  
Katelyn McCann ◽  
Evan Conaway ◽  
...  
Keyword(s):  
Innate Immune ◽  
Receptor Signaling ◽  
Mucosal Homeostasis ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages
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